CT-365: The Evaluation of Haematological and Biochemistry Parameters in COVID-19 Patients as a Predictive Factor for Unfavourable Evolution
Viola Maria PopovLelia IliescuMarius loan BaleaMihaela AndreescuMihaela PopescuOana PătrinoiuGeanina OfiţeruClaudia DespanMeilin OmerSilvia IonM BaleaCatalina ParvuOana ConstantinJeanina ValceaAdriana BadeaAna Martínez RusMihaela NiculaeAndreea CalenAndra GrigorieValentin NedelcuDaniela GologanuD. Georgescu
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Hematology
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Ferritin, an iron homeostasis protein, has important functions in transition and storage of toxic metal ions. In this study, the full-length cDNA of ferritin was isolated from Dendrorhynchus zhejiangensis by cDNA library and RACE approaches. The higher similarity and conserved motifs for ferritin were also identified in worm counterparts, indicating that it belonged to a new member of ferritin family. The temporal expression of worm ferritin in haemocytes was analyzed by RT-PCR, and revealed the ferritin could be induced by Cd2+, Pb2+ and Fe2+. The heavy metal binding activity of recombinant ferritin was further elucidated by atomic force microscopy (AFM). It was observed that the ferritin protein could form a chain of beads with different size against three metals exposure, and the largest one with 35∼40 nm in height was identified in the Cd2+ challenge group. Our results indicated that worm ferritin was a promising candidate for heavy metals detoxification.
Detoxification
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2019-20 coronavirus outbreak
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생체 내에 있어서 AsA 대사와 철 대사는 상호 밀접하게 연결되어 있다고 생각하여, 본 연구에서는 철단백질의 하나인 ferritin을 이용해서 AsA와의 상호작용의 유무를 조사하였다. Ferritin으로부터 철의 유리를 측정하기 위하여 ferrozine을 사용하여 AsA에 의한 ferritin으로부터 철의 유리를 흡광도 562 ㎚에서 Fe(ferrozine)₃^(2+)의 형태로 측정하는 방법을 사용하였다. 호기적 및 혐기적 조건 하에서 AsA에 의한 영향을 살펴본 결과, ferritin으로부터 철의 유리에 대해서 AsA의 농도 및 시간의 증가에 의존하는 것을 알 수 있었다. 또한 ferritin으로부터 철의 유리에 있어서 산소의 영향을 살펴본 결과, 가시부영역의 흡수 스펙트럼변화의 측정 결과에 의해 호기적 및 혐기적 조건 하 모두에서 ferritin으로부터 철의 유리를 확인하여 산소의 영향이 나타났고, 혐기적 조건하에서 보다 호기적 조건 하에서의 ferritin으로부터 철의 유리가 증가하는 것이 확인되었다. 즉, ferritin으로부터 철을 유리하는데 O₂-가 관여할 가능성이 나타났다. 그러나, 본 연구 결과에서 반응시간 1시간 후의 호기적 및 혐기적 조건 하에서 562 ㎚에서의 흡광도를 살펴본 결과 호기적 조건 하에서 유리된 철의 50% 이상이 AsA 자신에 의해, 나머지는 AsA와 산소분자와의 반응에 의해 생긴 O₂-에 의한다고 생각되어졌다. 지금까지 ferritin으로부터 철의 유리는 O₂-에 의한 것이라는 보고가 많았지만, 이 결과에 의해 ferritin으로부터 철의 유리에 O₂-가 관여하지만, 그것과 같은 정도 혹은 그 이상 AsA가 중요하다는 것이 밝혀졌다.
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Abstract The role of abnormal brain iron metabolism in neurodegenerative diseases is still insufficiently understood. Here, we investigate the molecular basis of the neurodegenerative disease hereditary ferritinopathy (HF), in which dysregulation of brain iron homeostasis is the primary cause of neurodegeneration. We mutagenized ferritin’s three-fold pores (3FPs), i.e. the main entry route for iron, to investigate ferritin’s iron management when iron must traverse the protein shell through the disrupted four-fold pores (4FPs) generated by mutations in the ferritin light chain (FtL) gene in HF. We assessed the structure and properties of ferritins using cryo-electron microscopy and a range of functional analyses in vitro. Loss of 3FP function did not alter ferritin structure but led to a decrease in protein solubility and iron storage. Abnormal 4FPs acted as alternate routes for iron entry and exit in the absence of functional 3FPs, further reducing ferritin iron-storage capacity. Importantly, even a small number of MtFtL subunits significantly compromises ferritin solubility and function, providing a rationale for the presence of ferritin aggregates in cell types expressing different levels of FtLs in patients with HF. These findings led us to discuss whether modifying pores could be used as a pharmacological target in HF.
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Iron deficiency is a major public health problem in the world. Ferritin is being explored as a novel and natural strategy for iron supplementation. The objective of this study was to evaluate iron bioavailability from ferritin isolated from plant and animal sources. The stability of plant ferritin and animal ferritin and the effects of cooking and skim milk were studied by in vitro and in vivo digestion. Results from SDS‐PAGE and Western blot indicate that both plant ferritin and animal ferritin can resist digestion (both under acidic and moderately acidic conditions). Furthermore, ferritin was labelled with 59Fe and bioavailability of iron from ferritin was assessed by uptake into Caco‐2 cells. Our results indicate that iron is taken up from the ferritins and that iron bioavailability from soybean ferritin (rH‐1: rH‐2= 1:1) is the highest. These results may be explained by the binding of ferritin to Caco‐2 cells, which can be attributed to the interaction between ferritin and its putative receptor(s) at the surface of Caco‐2 cells. In conclusion, ferritin from plant and animal sources may be developed as an iron source.
Digestion
Dietary iron
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腎盂尿管癌6例, 膀胱癌36例, 前立腺癌14例および尿路悪性腫瘍術後例49例において尿中 ferritin, 尿細胞診, 尿中FDP, 尿中CEAを検討し, 以下の如き結果を得た.1) poor grade 群および advanced stage 例における尿中 ferritin 値は well 群, early stage 例に比し有意に高値を示した.2) 尿中 ferritin は尿細胞診, 尿中FDP, 尿中CEAに比し陽性率が低く, tumor marker としては適していなかつた.3) 前立腺癌患者において血中 ferritin と尿中 ferritin の間に有意の相関はみられなかつた. また放射線療法による血中 ferritin の上昇はみられなかつたが, 尿中 ferritin は全例著明な上昇を認めた. この事により尿中 ferritin の source は腫瘍よりの分泌および放射線による組織破壊による事が考えられた.4) 腎盂尿管癌のほとんどの症例に尿中 ferritin の著明な上昇を認め, この事より患側腎尿細管傷害も尿中 ferritin 増加に何らかの役割を果たしている事が示唆された.
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We highlight in this short article the side-effects of COVID-19 pandemic on the management of non-COVID patients, with potential detrimental and irreversible complications. We thus propose adjusted strategies to deal with both COVID and non−COVID patients.
2019-20 coronavirus outbreak
Pandemic
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Examination of the mechanism of intracellular iron recovery from lysosomally-degraded ferritin in vivo has been complicated by the continuous flux of cellular iron through ferritin molecules. Here we incubated human fibroblasts with cationic ferritin, a derivative of horse spleen ferritin, as a technique for delivering immunologically distinct ferritin molecules directly to lysosomes. Using this method, we found increased endogenous ferritin levels after the cellular degradation of cationic ferritin, demonstrating that cells can utilize lysosomal ferritin to produce increased cytosolic ferritin levels. Further, using an in vitro assay, we showed that isolated lysosomes degrade endogenous ferritin in a time- and temperature-dependent manner. These results are consistent with a model in which cytosolic ferritin is taken into the lysosomes and degraded. The solubilized iron from the ferric core could then be transported across the lysosomal membrane back into the cytosol.
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Two improved procedures were developed for activating ferritin so that the ferritin could be covalently linked to antibodies. One procedure involved use of a water-soluble carbodiimide and N-hydroxysuccinimide to prepare ferritin-containing activated esters. The other involved activation of the ferritin with excess glutaraldehyde. The ferritin-antibody conjugates prepared with the two procedures were shown to have a number of properties which made them suitable for locating antigenic components in cells.
Carbodiimide
Conjugate
Glutaraldehyde
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